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Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders

It has been found that soluble epoxide hydrolase (sEH; encoded by the EPHX2 gene) in the metabolism of polyunsaturated fatty acids (PUFAs) plays a key role in inflammation, which, in turn, plays a part in the pathogenesis of neuropsychiatric disorders. Meanwhile, epoxy fatty acids such as epoxyeicos...

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Autores principales: Shan, Jiajing, Hashimoto, Kenji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099663/
https://www.ncbi.nlm.nih.gov/pubmed/35563342
http://dx.doi.org/10.3390/ijms23094951
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author Shan, Jiajing
Hashimoto, Kenji
author_facet Shan, Jiajing
Hashimoto, Kenji
author_sort Shan, Jiajing
collection PubMed
description It has been found that soluble epoxide hydrolase (sEH; encoded by the EPHX2 gene) in the metabolism of polyunsaturated fatty acids (PUFAs) plays a key role in inflammation, which, in turn, plays a part in the pathogenesis of neuropsychiatric disorders. Meanwhile, epoxy fatty acids such as epoxyeicosatrienoic acids (EETs), epoxyeicosatetraenoic acids (EEQs), and epoxyeicosapentaenoic acids (EDPs) have been found to exert neuroprotective effects in animal models of neuropsychiatric disorders through potent anti-inflammatory actions. Soluble expoxide hydrolase, an enzyme present in all living organisms, metabolizes epoxy fatty acids into the corresponding dihydroxy fatty acids, which are less active than the precursors. In this regard, preclinical findings using sEH inhibitors or Ephx2 knock-out (KO) mice have indicated that the inhibition or deficiency of sEH can have beneficial effects in several models of neuropsychiatric disorders. Thus, this review discusses the current findings of the role of sEH in neuropsychiatric disorders, including depression, autism spectrum disorder (ASD), schizophrenia, Parkinson’s disease (PD), and stroke, as well as the potential mechanisms underlying the therapeutic effects of sEH inhibitors.
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spelling pubmed-90996632022-05-14 Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders Shan, Jiajing Hashimoto, Kenji Int J Mol Sci Review It has been found that soluble epoxide hydrolase (sEH; encoded by the EPHX2 gene) in the metabolism of polyunsaturated fatty acids (PUFAs) plays a key role in inflammation, which, in turn, plays a part in the pathogenesis of neuropsychiatric disorders. Meanwhile, epoxy fatty acids such as epoxyeicosatrienoic acids (EETs), epoxyeicosatetraenoic acids (EEQs), and epoxyeicosapentaenoic acids (EDPs) have been found to exert neuroprotective effects in animal models of neuropsychiatric disorders through potent anti-inflammatory actions. Soluble expoxide hydrolase, an enzyme present in all living organisms, metabolizes epoxy fatty acids into the corresponding dihydroxy fatty acids, which are less active than the precursors. In this regard, preclinical findings using sEH inhibitors or Ephx2 knock-out (KO) mice have indicated that the inhibition or deficiency of sEH can have beneficial effects in several models of neuropsychiatric disorders. Thus, this review discusses the current findings of the role of sEH in neuropsychiatric disorders, including depression, autism spectrum disorder (ASD), schizophrenia, Parkinson’s disease (PD), and stroke, as well as the potential mechanisms underlying the therapeutic effects of sEH inhibitors. MDPI 2022-04-29 /pmc/articles/PMC9099663/ /pubmed/35563342 http://dx.doi.org/10.3390/ijms23094951 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Shan, Jiajing
Hashimoto, Kenji
Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders
title Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders
title_full Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders
title_fullStr Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders
title_full_unstemmed Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders
title_short Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders
title_sort soluble epoxide hydrolase as a therapeutic target for neuropsychiatric disorders
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099663/
https://www.ncbi.nlm.nih.gov/pubmed/35563342
http://dx.doi.org/10.3390/ijms23094951
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AT hashimotokenji solubleepoxidehydrolaseasatherapeutictargetforneuropsychiatricdisorders